There seems to be an absence of agreement about how aggressively to treat pre-diabetes. Would so appreciate thoughts about this.
Have read here that ideally A1C should be 5 or below. Mine is higher: about 5.6 but up to 5.9 on Repatha. Fasting blood glucose about 100 +/- 10, occasionally higher, but in the “pre” range. I have been on 1000 Metformin for a while, plus several supplements that supposedly help control blood glucose.
My FBG has been at approximately this level for over a decade, long before I started cholesterol meds. Insulin has been low – about 3 to 4 u/U/mL. My PCP says that these levels might just be “normal” for me. I have been reading about glucokinase mody, which is an inherited deficiency in glucose sensing that is not really a danger and doesn’t usually progress. But I do not know if that is what’s going on here.
Repatha and Ezetimibe have gotten LDL to about 49 and APOB to 52. I have wanted to be on Repatha because Lp(a) was 40 (now about 27), and there is a bit of plaque (CAC score 0.96). I am basically healthy, low trigs, high HDL and good function.
Taking many supplements, but not rapamycin.
Given all this, trying to decide whether to add an SGLT-2.
Would so appreciate thoughts, questions, suggestions.
Josh
#2
I think you might as well aggressively treat since the treatments like acarbose, sglt2, GLP1 (maybe metformin) all seem to provide a myriad of health and lifespan benefits in all tests. Personally I do acarbose (mouse lifespan extension) and GLP1 (benefit for almost all diseases in humans it seems).
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Beth
#3
If I recall you are fairly slender, if so, you might not be able to use enough glp1 to help, but perhaps a tiny dose can provide some benefit?
Incase it’s useful, I’ll share that I’m fairly sensitive to things and I take an sglt2 and acarbose and do really well on both. I stopped taking metformin as it didn’t do that much for me and I was told it might interfere with my goals of building muscle.
My A1C is fine, but these are for long term health and to control my abnormal glucose spikes as seen on my CGM. Metformin helped somewhat, but sglt2 helps significantly more.
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I wouldn’t put this goal too high on a pedestal. A 5.0 hba1c is the equivalent of 96.8 average glucose assuming normal red blood cell lifespan. 96.8 mg/dl is a reasonably good fasting glucose number so to get an average of 96.8 you need a fasting glucose in the 80’s (a rough guess) and few hours above 120 after meals. Hba1c of 5.0 is great if you have it naturally but to force it down with drugs can lead to unpleasant side effects. Low blood sugar is a poor way to live in my opinion.
Stay under 5.6 is what I think. Focus on stress management and good sleep, and a whole food diet of course. Use drugs if necessary but not in place of lifestyle improvements.
The medical experts should weigh in to keep the “optimal” goal setting from running amok.
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AIUI, SGLT2-i, Acarbose and possibly even metformin are unlikely to make a huge difference at your A1c. GLP-1 probably would due to their enhancement of insulin secretion. Still, I would probably try adding SGLT2, acarbose and a GLP-1 if possible if I were in your position.
For me, this combination did not change my A1c, but it did improve my CGM metrics which you can read about here.
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Beth
#6
Good morning Deborah,
I am watching the Rich Roll podcast released today interviewing Valter Longo. I’m reminded by him that his FMD (Prolon) has done wonders for people with diabetes. Because it can do other great things for one’s health, it occurred to me to recommend it to you.
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Thank you Beth. Will check it out.
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You haven’t mentioned your diet, which is a key component. I have been low-carb for many years yet my fasting glucose is usually around 105-110. While that qualifies me as “prediabetes” my BG never rises much above that level during the day or after meals. So there are a number of theories for this: your body needs more glucose than you are consuming so it makes it through gluconeogenesis, or what is called the dawn phenomenon. Another explanation is sleep issues may cause the release of norepinephrine. My view and my current doctor’s view is that this level of fasting glucose is nothing to worry about unless and until it starts rising.
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LukeMV
#9
This study from April 2024 showed less cardiovascular risk in men (but not women) between 5-5.4% compared to 5.5-5.9%, but 6% and up is much worse.
https://www.ahajournals.org/doi/10.1161/JAHA.123.031095
Personally, I like to be aggressive and keep it between 4.9-5.2%.
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Jo,
You are right, it is hard to show much benefit (but there might be some) to having a HbA1C of 5.6% or less vs. 5.7%. Certainly going higher is going to add risk.
Insulin sensitivity is an important component, but I have a lot of patients that with aging, remain insulin sensitive, do everything right on diet/exercise/weight/visceral fat, but have hyperglycemia and HbA1C creeping up.
There is the toxic effect of the glucose on blood vessels, and separately of high insulin (in those who are insulin resistant). It’s not only heart disease, it is white matter change in the brain (which so many of my patients who have ignored getting their ApoB optimal have, and think a CT Cardiac Calcium score of 0 means all is okay). Our last major item to manage is blood pressure and get this optimal. Omega 3 index optimal and Vitamin D optimal.
It’s multiple items, and if all the others are perfect and one has a HbA1C of 5.7% I doubt there is evidence of benefit with treatment (which doesn’t mean there isn’t benefit).
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Josh
#11
I’m a proponent of trying to restore youthfulness and health instead of only longevity. Levels in youth are under 5.4% (5-5.3%). Note that alcoholism and other diseases can lower hba1c so that is one reason why we do not see lower all cause mortality at under 5% for example. We always see these u-shaped curves like with BMI as well. Doesn’t mean you won’t be healthier with a BMI like 22 when lowest mortality is 26-28 as long as you get there from eating healthy and not cancer etc.
Looks like there’s a whole topic on this Optimal HBA1c Levels (Lustgarten)
(too) High RBC turnover also lowers hba1c without lowering avg glucose
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Broccoli extract reduces blood sugar in pre-diabetics. Here’s how you prepare it to maximize its benefit.
Published this week, a clinical trial with 89 pre-diabetic participants found that consuming broccoli extract (150µl of Sulphoraphane per dose) reduced fasting blood glucose by 0.3 mmol/l in 12 weeks.
In detail
- Active Sulforaphane inhibits the synthesis and release of sugar by the liver (gluconeogenesis) similar to metformin, the first line of treatment for pre diabetes.
- The effect was mediated by the gut-bacteria with individuals showing a larger response (0.4 mmol/l reduction in fasting blood sugar) showing a distinct gut bacteria composition.
- Genomic analysis revealed higher levels of a transcription factor responsible for activating the expression of a bacterial enzyme that can turn inactive sulforaphane into its biologically active form (known as isothiocyanate), which has the glucose lowering effect.
Keep in mind: not only diabetics and pre-diabetics can benefit from blood sugar reduction, lowering your blood sugar levels within normal range, and minimizing fluctuations vastly improves your metabolic health and helps preventing all age-related diseases.
Tip for optimal broccoli prep: Chop your broccoli into small pieces and let it sit for 40 minutes before steaming or boiling.
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Broccoli contains Sulforaphane as a precursor linked to a special type of sugar (myrosinase), broccoli also has the enzyme (myrosinase) that breaks the sulforaphane free and activates it .
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The enzyme is activated by the broccoli being damaged (as a defense mechanism of the plant against herbivores in the wild) but is destroyed by cooking, hence chopping your broccoli and giving it time before cooking is the best way to enrich your fresh broccoli in active Sulforaphane before cooking.
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If you don’t have time to wait, adding mustard seed powder (which contains myrosinase) to cooked broccoli can restore sulforaphane formation.
Effect of broccoli sprout extract and baseline gut microbiota on fasting blood glucose in prediabetes: a randomized, placebo-controlled trial
More effective treatments are needed for impaired fasting glucose or glucose intolerance, known as
prediabetes. Sulforaphane is an isothiocyanate that reduces hepatic gluconeogenesis in individuals with type 2 diabetes and is well tolerated when provided as a broccoli sprout extract (BSE). Here we report a randomized, double-blind, placebo-controlled trial in which drug-naive individuals with prediabetes were treated with BSE (n = 35) or placebo (n = 39) once daily for 12 weeks. The primary outcome was a 0.3 mmol l−1reduction in fasting blood glucose compared with placebo from baseline to week 12. Gastro-intestinal side effects but no severe adverse events were observed in response to treatment. BSE did not meet the prespecified primary outcome, and the overall effect in individuals with prediabetes was a 0.2 mmol l−1 reduction in fasting blood glucose (95% confidence interval −0.44 to −0.01; P = 0.04). Exploratory analyses to identify subgroups revealed that individuals with mild obesity, low insulin resistance and reduced insulin secretion had a pronounced response (0.4 mmol l−1 reduction) and were consequently referred to as responders. Gut microbiota analysis further revealed an association between baseline gut microbiota and pathophysiology and that responders had a different gut microbiota composition. Genomic analyses confirmed that responders had a higher abundance of a Bacteroides -encoded transcriptional regulator required for the conversion of the inactive precursor to bioactive sulforaphane. The abundance of this gene operon correlated with sulforaphane serum concentration. These findings suggest a combined influence of host pathophysiology and gut microbiota on metabolic treatment response, and exploratory analyses need to be confirmed in future trials. ClinicalTrials.gov registration: NCT03763240.
open access:
https://www.nature.com/articles/s41564-025-01932-w
Related Threads:
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I want to lower my A1C by a few points. My goal is to increase muscle mass (and lose fat mass) over the coming months to help with this. A new review paper related to this:
As the prevalence of obesity and metabolic disease continues to climb, the need for effective therapeutic interventions remains high. The growth of skeletal muscle (SkM) greatly influences systemic metabolism across the whole body, making this tissue an important therapeutic target to combat the rise of metabolic dysfunction.
Skeletal muscle growth to combat diabetes and obesity: the potential role of muscle-secreted factors
https://onlinelibrary.wiley.com/doi/10.1002/oby.24223
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Given your wonderfully low insulin level, I’m wondering if your HbA1c is painting an accurate picture. Why? Because the whole premise of using HbA1c as a direct metric for measuring blood glucose control is built on a fallacy. What’s that? The (invalid) assumption that everybody has RBCs with the same lifespan. If you’re pretty healthy, it’s quite possible that your RBCs might be a bit longer-lived than the average person’s. Which means that there’s more time during their lifespan for them to accumulate glucose. Remember, HbA1c is an “area under the curve” measure that reflects both your varying blood glucose levels AND the amount of time that that glucose has to get into a red cell and bind to its hemoglobin.
What to do? Get a continuous glucose monitor and collect some more data. Perhaps you really do have a problem, either with early morning glucose elevations or with prolonged elevated post-prandial glucose elevations. If so… yes, you have a problem – but it might not be typical prediabetes. With your wonderfully low insulin levels, it’s much more likely to be a case of inadequate insulin production (e.g. maybe a form of MODY) than it is a problem with insulin resistance. And if not… well, maybe relax a little.
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Thanks for your response. Because the FBG has been in the range of 100 mostly +/- 10, for years, with low insulin and low c peptide I am inclined to believe what I have is glucokinase mody. Will continue to monitor but have calmed down about all this.
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Perhaps of interest for people interested in this thread:
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I agree with this. Don’t think adding SGLT2 would be beneficial for you.
The real question is how well do you tolerate sugar, and do you actually have insulin resistance. Based on your posts so far, it seems that you don’t have insulin resistance.
However, I also think you should try wearing a continuous glucose monitor. Honestly, it’s really insightful, at least to know your rough daily patterns, what happens when you sleep/exercise, and how you respond to certain food. My wife and I did it together, and the results seem highly individual. Bread and pasta sent her glucose from 80 up to 150, but barely affected me. However, if I eat the smallest amount of fruit (apple, grapes etc) mine went shooting up. For me, wearing one for 2 weeks every year has been useful to help modify my behaviors, knowing that certain foods are problematic or not.
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What I find interesting that a CGM tells me is how my body’s glucose feedback systems change quite signficantly when I make significant changes in inputs. Such as a high rapamycin dose, not surprising, but you can see the feedback systems adjust. This is also obvious in the blood markers, but the CGM is much more understandable.
On the other hand my Dexcom one+ does seem to get a bit unreliable in the last couple of days. Sadly I could not switch continuously over the weekend because my replacement implant failed and I then didn’t have a spare. This means I cannot properly compare one trend to another.
The price has come down. In the UK it is now £35 for 10 days.
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